Fragile X for the obstetrician and gynecologist

The fragile X syndrome is the most common cause of genetic-based mental retardation. Mutations of the fragile X gene occur as a spectrum of genetic changes. Both premutations and full mutations are associated with a variety of clinical syndromes including mental retardation, autism, premature ovarian aging and failure, and fragile X-associated tremor and ataxia. The mechanisms of inheritance of fragile X gene mutations are complex in that the mutation can change during transmission from one generation to the next. Womens' healthcare providers should be aware of the association of fragile X premutations with early ovarian aging and premature ovarian failure. Women with the fragile X premutation are at increased risk of having offspring with fragile X syndrome. The American College of Obstetrics and Gynecology recommends that women with an elevated level of follicle-stimulating hormone before the age of 40 years without a known cause; any child with a developmental delay, mental retardation, autism or autistic behavior of unknown etiology; and patients with a family history of mental retardation should be screened for fragile X. Prenatal testing can also be performed on known carriers of a fragile X premutation.